The present invention relates to devices and methods for assisting ionisation of liquid samples for subsequent mass spectrometer analysis.
Mass spectrometers are often used to analyse the masses of components of liquid samples obtained from analysis devices such as liquid chromatographs. Mass spectrometers require that the component sample that is to be analysed be provided in the form of free ions and it is usually necessary to evaporate the liquid samples in order to produce a vapour of ions. This is commonly achieved by using electrospray ionisation. In electrospray ionisation (ESI) a spray is generated by applying a voltage (in the order of 2-3 kV) to a hollow needle through which the liquid sample can freely flow. The inlet orifice to the mass spectrometer is given a lower potential, for example 0V, and an electrical field is generated from the tip of the needle to the orifice of the mass spectrometer. The electrical field attracts the positively charge species in the fluid which accumulate in the meniscus of the liquid at the tip of the needle. The negatively charged species in the fluid are neutralised. This meniscus extends towards the oppositely charged orifice and forms a xe2x80x9cTaylor conexe2x80x9d. When the attraction between the charged species and the orifice exceeds the surface tension of the tip of the Taylor cone, droplets break free from the Taylor cone and fly in the direction of the electrical field lines towards the orifice. During the flight towards the orifice the liquid in the droplets evaporates and the net positive charge in the droplet increases. As the net charge increases, the columbic repulsion between the like charges in the droplet also increases. When the repulsion force between these like charges exceeds the liquid surface tension in the droplet, the droplet bursts into several smaller droplets. The liquid in these droplets in turn evaporates and these droplets also burst. This occurs several times during the flight towards the orifice.
There are two theories about how the analytes in the liquid enter the vapour phase as free ions. In the first theory, known a the ion desorption method, it is assumed that when the droplet size reduces to a certain small volume, the repulsion between the charged molecules in the droplet will cause the molecules to penetrate the liquid surface and enter the vapour phase. As the droplets continue to shrink, more and more molecules enter the vapour phase.
In the second theory, known as the charged residue mechanism, it is assumed that there comes a stage where each droplet is very small and each one only contains one analyte molecule. As the last molecules of solvent, usually water, evaporate from the droplet, the excess of positive charges in the water is transferred to the analyte molecule which is now in the vapour phase. For the purposes of the invention, it does not matter which theory is correct. A problem with electrospray ionisation is that at high flow rates (e.g. over about 10 microliters per minutes) the average size of the droplets increases. Many of these droplets hit the inlet plate and are neutralised before the molecules of interest have entered the vapour phase. This means that these molecules will not be analysed which leads to reduced sensitivity.
U.S. Pat. No. 4,935,624 teaches an improved method and apparatus for forming ions at atmospheric pressure from a liquid and for introducing the ions into a mass analyser. It attempts to overcome the disadvantage of electrospray ionisation when used for flows much greater than 10 microliters per minute e.g. up to about 2000 microliters per minute. In this document, the apparatus for forming ions comprises a capillary tube that receives the liquid from a liquid chromatograph, and a thermal energy means for directly or indirectly heating the liquid in the capillary tube. The thermal energy means could be provided by electrically resistive heating, piezoelectric heating, ultrasonic heating, infrared heating, microwave heating and conduction from gas heating. The addition of extra heat disperses the droplets into a fine mist. This device suffers from the disadvantage that the heating of the liquid takes place in a capillary tube which means that heating of the droplets is not homogeneousxe2x80x94as the capillary wall inevitably is warm some of the heating takes place from the outside of the droplet towards the inside of the droplet due to the contact between the droplet and the warm capillary wall. Therefore some of the liquid may boil while the rest of the liquid is barely warmed. This is disadvantageous because if the liquid boils then the electrochemical reaction that generates the excess of positive charges which promotes the spray will not occur, while if the liquid is barely heated then the droplets will not evaporate quickly enough on their flights to the orifice.
The purpose of the present invention is to provide devices and methods which overcome the disadvantages of the prior art devices and methods for assisting the ionisation of liquid samples for subsequent mass spectrometer analysis. This is achieved by means of a device having the characterising features of claim 1 and a method having the characterising features of claim 4.
In particular, in a first embodiment of a device in accordance with the present invention, a microwave-emitting device is positioned between the spray tip of a tube that receives the liquid from a source such as a liquid chromatograph and the target orifice. In this way the droplets are heated in a homogeneous way by the microwaves emitted from the microwave-emitting device.